Platelets (Basic)
Novel interactions in platelet biology: CLEC-2/podoplanin and laminin/GPVI

https://doi.org/10.1111/j.1538-7836.2009.03372.xGet rights and content
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Summary

We have identified a novel platelet membrane protein, CLEC-2 as a receptor for rhodocytin, a platelet-activating snake venom. CLEC-2 is specifically expressed in platelets and megakaryocytes, and has an atypical ITAM, which undergoes tyrosine phosphorylation by Src kinases, resulting in downstream signaling including Syk, SLP-76 and PLCγ2. We found that CLEC-2 is the receptor for podoplanin, a sialoglycoprotein implicated in tumor-induced platelet aggregation and tumor metastasis. VWF bridges exposed collagen, at damaged vessels, to GPIb. Subsequently, GPVI binds to collagen, leading to integrin α2β1 activation. We found that platelets adhere to laminin, another major ECM component, through integrin α6β1, and are activated through GPVI. This is the first report on GPVI having a ligand, laminin, other than collagen. Laminin also interacts with VWF, leading to platelet adhesion via GPIb under sheer stress. The redundancy of platelet interactions with laminin and with collagen may serve to promote hemostasis at sites of damaged vessels.

Keywords

CLEC-2
collagen
GPVI
laminin
platelet
podoplanin

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